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Inactivation of the Akt/FOXM1 Signaling Pathway by Panobinostat Suppresses the Proliferation and Metastasis of Gastric Cancer Cells

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Histone deacetylase (HDAC) inhibitors are a new class of cytostatic agents available for the treatment of various cancers and diseases. Although numerous clinical and pre-clinical trials on...

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Autores principales: Lee, Na-Ri, Kim, Da-Yeah, Jin, Hua, Meng, Ruoyu, Chai, Ok Hee, Kim, Seong-Hun, Park, Byung-Hyun, Kim, Soo Mi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199011/
https://www.ncbi.nlm.nih.gov/pubmed/34073071
http://dx.doi.org/10.3390/ijms22115955
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author Lee, Na-Ri
Kim, Da-Yeah
Jin, Hua
Meng, Ruoyu
Chai, Ok Hee
Kim, Seong-Hun
Park, Byung-Hyun
Kim, Soo Mi
author_facet Lee, Na-Ri
Kim, Da-Yeah
Jin, Hua
Meng, Ruoyu
Chai, Ok Hee
Kim, Seong-Hun
Park, Byung-Hyun
Kim, Soo Mi
author_sort Lee, Na-Ri
collection PubMed
description Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Histone deacetylase (HDAC) inhibitors are a new class of cytostatic agents available for the treatment of various cancers and diseases. Although numerous clinical and pre-clinical trials on the anticancer effects of panobinostat have been conducted, only a few reports have investigated its efficacy in gastric cancer. The present study aimed to investigate the effects of panobinostat in gastric cancer cells. Panobinostat significantly inhibited the cell viability and proliferation of the gastric cancer cell lines SNU484 and SNU638 in a dose-dependent manner; it reduced the colony-forming ability of these cells. Moreover, it induced apoptosis as indicated by increased protein levels of cleaved poly ADP-ribose polymerase and cleaved caspase-3. Panobinostat induced the G2/M cell cycle arrest in SNU484 and SNU638 cells and subsequently decreased the G2/M phase regulatory-associated protein expression of p-Wee1, Myt1, and Cdc2. Furthermore, panobinostat significantly inhibited the metastasis of SNU484 and SNU638 cells by regulating the expression of MMP-9 and E-cadherin. Further, it decreased the protein levels of p-Akt and forkhead box protein M1 (FOXM1). These effects were reversed by the Akt agonist SC79 and were accelerated by the Akt inhibitor LY2940002. Moreover, tumor growth in xenograft animal experiments was suppressed by panobinostat. These results indicated that panobinostat inhibits the proliferation, metastasis, and cell cycle progression of gastric cancer cells by promoting apoptosis and inactivating Akt/FOXM1 signaling. Cumulatively, our present study suggests that panobinostat is a potential drug for the treatment of gastric cancer.
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spelling pubmed-81990112021-06-14 Inactivation of the Akt/FOXM1 Signaling Pathway by Panobinostat Suppresses the Proliferation and Metastasis of Gastric Cancer Cells Lee, Na-Ri Kim, Da-Yeah Jin, Hua Meng, Ruoyu Chai, Ok Hee Kim, Seong-Hun Park, Byung-Hyun Kim, Soo Mi Int J Mol Sci Article Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Histone deacetylase (HDAC) inhibitors are a new class of cytostatic agents available for the treatment of various cancers and diseases. Although numerous clinical and pre-clinical trials on the anticancer effects of panobinostat have been conducted, only a few reports have investigated its efficacy in gastric cancer. The present study aimed to investigate the effects of panobinostat in gastric cancer cells. Panobinostat significantly inhibited the cell viability and proliferation of the gastric cancer cell lines SNU484 and SNU638 in a dose-dependent manner; it reduced the colony-forming ability of these cells. Moreover, it induced apoptosis as indicated by increased protein levels of cleaved poly ADP-ribose polymerase and cleaved caspase-3. Panobinostat induced the G2/M cell cycle arrest in SNU484 and SNU638 cells and subsequently decreased the G2/M phase regulatory-associated protein expression of p-Wee1, Myt1, and Cdc2. Furthermore, panobinostat significantly inhibited the metastasis of SNU484 and SNU638 cells by regulating the expression of MMP-9 and E-cadherin. Further, it decreased the protein levels of p-Akt and forkhead box protein M1 (FOXM1). These effects were reversed by the Akt agonist SC79 and were accelerated by the Akt inhibitor LY2940002. Moreover, tumor growth in xenograft animal experiments was suppressed by panobinostat. These results indicated that panobinostat inhibits the proliferation, metastasis, and cell cycle progression of gastric cancer cells by promoting apoptosis and inactivating Akt/FOXM1 signaling. Cumulatively, our present study suggests that panobinostat is a potential drug for the treatment of gastric cancer. MDPI 2021-05-31 /pmc/articles/PMC8199011/ /pubmed/34073071 http://dx.doi.org/10.3390/ijms22115955 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Na-Ri
Kim, Da-Yeah
Jin, Hua
Meng, Ruoyu
Chai, Ok Hee
Kim, Seong-Hun
Park, Byung-Hyun
Kim, Soo Mi
Inactivation of the Akt/FOXM1 Signaling Pathway by Panobinostat Suppresses the Proliferation and Metastasis of Gastric Cancer Cells
title Inactivation of the Akt/FOXM1 Signaling Pathway by Panobinostat Suppresses the Proliferation and Metastasis of Gastric Cancer Cells
title_full Inactivation of the Akt/FOXM1 Signaling Pathway by Panobinostat Suppresses the Proliferation and Metastasis of Gastric Cancer Cells
title_fullStr Inactivation of the Akt/FOXM1 Signaling Pathway by Panobinostat Suppresses the Proliferation and Metastasis of Gastric Cancer Cells
title_full_unstemmed Inactivation of the Akt/FOXM1 Signaling Pathway by Panobinostat Suppresses the Proliferation and Metastasis of Gastric Cancer Cells
title_short Inactivation of the Akt/FOXM1 Signaling Pathway by Panobinostat Suppresses the Proliferation and Metastasis of Gastric Cancer Cells
title_sort inactivation of the akt/foxm1 signaling pathway by panobinostat suppresses the proliferation and metastasis of gastric cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199011/
https://www.ncbi.nlm.nih.gov/pubmed/34073071
http://dx.doi.org/10.3390/ijms22115955
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